Advances in next-generation sequencing (NGS) technologies have tremendously reduced sequencing costs, providing us with unprecedented opportunities to elucidate the trajectory of vertebrate genome evolution and the origin of complex traits in different species using comparative genomics. The insights from such comparative genomic analysis can in turn help us annotate the human genome and identify key variants related to human

disease mechanisms. However, the large number of genomes being sequenced and the challenges caused by NGS have underlined urgent needs for new computational

innovations to facilitate the next-generation comparative genomic research. In this talk, I will introduce several works that we developed recently to address pressing challenges in genome annotation and genome comparisons with the goal to accelerate our understanding of the genomic differences and gene regulation variations that result in phenotypic diversity.